Amines from nitrile reduction

Primary amine formation is equally well promoted in alkaline medium, e.g., aqueous ethanolic NaOH solution, that selectively poisons the catalyst for hydrogenolysis reactions. However, saturated NH3/alcohol solutions best afford almost quantitative yields of primary amines from catalytic reduction of nitriles. Ammonia adds to imine 1 to give a 1,1-diamine, which is hydrogenolyzed to the primary amine. In the presence of NHj, finely divided Ni can be used, platinized finely divided Ni for the hydrogenation of hindered nitriles, and rhodium-on-alumina for sensitive compounds. Mild reduction of 3-indoleacetonitrile to tryptamine [equation (c)] is effected at RT over 5% rhodium-on-alumina in 10% ethanolic NH3 with little side reaction , and branched chain amino sugars are conveniently prepared using this selective hydrogenation [equation (d)] . 

Alcohols from carboxylic acid esters Bouveault-Blanc reduction s. 1, 64, 75 2, 89/90 new procedures s. 3, 49/50 also amines from nitriles s. 4, 89 Preparation of anhydrous alcohols s. 4,90 Alcohols from ethylenecarboxylic acid esters s. 4, 91 Hydroxyacetals from carbalkoxyacetals s. 4, 92 Acridines from acridones s. 2, 91 COOR -V CH2OH... 

Platinum-nickel-alumina Prim, amines from nitriles Partial and total reduction... 

Reductive pyrrolidine ring closure Prim, amines from nitriles N-Decarbobenzoxy lation... 

Amides may also be prepared by reduction of nitriles to amines followed by acylation. See section 103 (Amines from Nitriles)... 

Mesityl oxide refluxed 16 hrs. in water with a precipitated Ni-catalyst prepared from NiGl2 and Zn-dust in water isobutyl methyl ketone. Y 95%. - These convenient reductions do not require hydrogen. F. e., e.g. prim, amines from nitriles, s. K. Sakai and K. Watanabe, Bull. Chem. Soc. Japan W, 1548 (1967). 

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

Another type of reductive amination is shown in Figure 13-18. This reaction illustrates the formation of an amine from a ketone through the formation of an intermediate oxime. Figure 13-19 shows the conversion of a nitrile to an amine. (The nitrile can be formed by the action of cyanide ion, CN", on a halide via an Sf 2 mechanism.)... 

Amines are at the same low oxidation level as alcohols and consequently are easily prepared by reduction. Amides and nitriles are reduced efficiently by LAH to amines. Nitriles give only primary amines while amides give 1°, 2°, or 3° amines depending on the number of carbon substituents on the amide nitrogen. The advantage of this method is that amides are easy to prepare from acid chlorides and amines while nitriles are available by displacement reactions. 

Nitrile Reduction. The choice of catalyst and variations of the temperature, pressure, and concentration of ammonia can control the product mix of amines from hydrogenation of a nitrile. The reaction is shown in Reaction (22-56) ... 

Nonetheless, it was a fairly short step from octopus compounds to dendrimers, and the step was taken by Vogtle in the late 1970s when he attempted to use a cascade reaction to prepare a molecule of the dendrimer type that would now be considered a dendron rather than a fully developed dendrimer. It began with the addition of acrylonitrile to an amine, followed by reduction of the nitrile to amine. This was followed by a further reaction with acrylonitrile, and the process was repeated several times to yield highly branched macromolecules. There were initially problems with the reduction step but these were overcome, and the preparation of these polypropylene imine) dendrimers was later commercialized. 

Nitrilium salts (40 equation 10) can be prepared from nitriles and triethyloxonium fluoroborate. Early workers concluded that the nitrilium salts could be reduced to amines but that the reduction could not be stopped at the aldehyde (aldimine) stage.Later, it was demonstrated that reduction of the nitrilium salts with NaBH4 was rapid and did give the corresponding amine, but with triethylsilane yields of 60-90% of both aliphatic and aromatic aldehydes were obtained. Triethylsilane is a mild reagent which reduces carbocations but neutral compounds are generally not reduced and so overreduction is not a problem with this reagent. Formation of the nitrilium salts with triethyloxonium fluoroborate is slow but can be speeded up by the use of iron(III) chloride (Scheme 19). There were some notable exceptions to aldehyde formation with some aromatic nitriles. 

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